Childhood leukemia genetic bottleneck phenomenon related to TEL-AML1: The postulation by a mathematical model

Abstract

Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the prenatal origin discovery of leukemogenic chromosome translocations. The bottleneck is evidence that leukemia initiation, by in utero acquired chromosome translocations that generate functional fusion genes, is far more common than the incidence rate of corresponding leukemia. For childhood TEL-AML1 + acute lymphoblastic leukemia (ALL) this equates to approximately 100 times. Practically this means that among a hundred children born with TEL-AML1 fusion gene, only one child will later in its life develop ALL. The key data necessary for unraveling of this mystery were discovered in 2002. It was the level of TEL-AML1 + cells' frequency. The bottleneck is caused by the very low body TEL-AML1 + cell count. Only one out of a thousand B cells carries TEL-AML1 fusion gene. TEL-AML1 + body cell count is low because TEL-AML1 fusion is generated at cell level of 10- 3 to 10- 4 just during the late fetal lymphopoiesis i.e. after the 36th gestational week.